Immuno-modulator inter-alpha inhibitor proteins ameliorate complex auditory processing deficits in rats with neonatal hypoxic-ischemic brain injury.

Hypoxic-ischemic (HI) brain injury is recognized as a significant problem in the perinatal period, contributing to life-long language-learning and other cognitive impairments. Central auditory processing deficits are common in infants with hypoxic-ischemic encephalopathy and have been shown to predict language learning deficits in other at risk infant populations. Inter-alpha inhibitor proteins (IAIPs) are a family of structurally related plasma proteins that modulate the systemic inflammatory response to infection and have been shown to attenuate cell death and improve learning outcomes after neonatal brain injury in rats. Here, we show that systemic administration of IAIPs during the early HI injury cascade ameliorates complex auditory discrimination deficits as compared to untreated HI injured subjects, despite reductions in brain weight. These findings have significant clinical implications for improving central auditory processing deficits linked to language learning in neonates with HI related brain injury.

A randomized controlled trial testing an Internet delivered cost-benefit approach to weight loss maintenance.

Weight loss maintenance is a significant challenge in obesity treatment. During maintenance the "costs" of adhering to weight management behaviors may outweigh the "benefits." This study examined the efficacy of a novel approach to weight loss maintenance based on modifying the cost-benefit ratio. Individuals who achieved a 5% weight loss (N=75) were randomized to one of three, 10-month maintenance interventions. All interventions were delivered primarily via the Internet. The Standard arm received traditional weight maintenance strategies. To increase benefits, or rewards, for maintenance behaviors, the two cost-benefit intervention conditions received weekly monetary rewards for self-monitoring and social reinforcement via e-coaching. To decrease behavioral costs (boredom) and increase novelty, participants in the cost-benefit conditions also monitored different evidence-based behaviors every two weeks (e.g., Weeks 1 & 2: steps; Week 3 & 4: red foods). The primary difference between the cost-benefit interventions was type of e-coach providing social reinforcement: Professional (CB Pro) or Peer (CB Peer). Study procedures took place in Providence, RI from 2013 to 2014. Retention was 99%. There were significant group differences in weight regain (p=.01). The Standard arm gained 3.5±5.7kg. In contrast, participants in CB Pro and CB Peer lost an additional 1.8±7.0kg and 0.5±6.4kg, respectively. These results suggest that an Internet delivered cost-benefit approach to weight loss maintenance may be effective for long-term weight control. In addition, using peer coaches to provide reinforcement may be a particularly economic alternative to professionals. These data are promising and provide support for a larger, longer trial.

Effects of inter-alpha inhibitor proteins on neonatal brain injury: Age, task and treatment dependent neurobehavioral outcomes.

Hypoxic-ischemic (HI) brain injury is frequently associated with premature and/or full term birth related complications. HI injury often results in learning and processing deficits that reflect widespread damage to an extensive range of cortical and sub-cortical brain structures. Further, inflammation has been implicated in the long-term progression and severity of HI injury. Recently, inter-alpha inhibitor proteins (IAIPs) have been shown to attenuate inflammation in models of systemic infection. Importantly, preclinical studies of neonatal HI injury and neuroprotection often focus on single time windows of assessment or single behavioral domains. This approach limits translational validity, given evidence for a diverse spectrum of neurobehavioral deficits that may change across developmental windows following neonatal brain injury. Therefore, the aims of this research were to assess the effects of human IAIPs on early neocortical cell death (72h post-insult), adult regional brain volume measurements (cerebral cortex, hippocampus, striatum, corpus callosum) and long-term behavioral outcomes in juvenile (P38-50) and adult (P80+) periods across two independent learning domains (spatial and non-spatial learning), after postnatal day 7 HI injury in rats. Here, for the first time, we show that IAIPs reduce acute neocortical neuronal cell death and improve brain weight outcome 72h following HI injury in the neonatal rat. Further, these longitudinal studies are the first to show age, task and treatment dependent improvements in behavioral outcome for both spatial and non-spatial learning following systemic administration of IAIPs in neonatal HI injured rats. Finally, results also show sparing of brain regions critical for spatial and non-spatial learning in adult animals treated with IAIPs at the time of injury onset. These data support the proposal that inter-alpha inhibitor proteins may serve as novel therapeutics for brain injury associated with premature birth and/or neonatal brain injury and highlight the importance of assessing multiple ages, brain regions and behavioral domains when investigating experimental treatment efficacy.